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Biomedical subjects

S R Miller

Publications and source records attributed to S R Miller.

At least 19 recordsLinked to original sources

Small incision nonendoscopic browlift.

PURPOSE: To determine the efficacy of a nonendoscopic brow/forehead lift. METHODS: Case series of 12 patients. Small scalp and upper eyelid blepharoplasty incisions were used to elevate the brows/forehead and perform protractor myectomy. RESULTS: All patients achieved an aesthetically pleasing eyebrow and forehead lift with reduction of vertical and horizontal glabellar creases. Complications included one patient who experienced prolonged ecchymosis after corrugator muscle resection and one patient who had asymmetric lid folds after surgery. The length of follow-up ranged from 9 to 35 months. CONCLUSIONS: The small incision nonendoscopic browlift technique provides a useful alternative to the endoscopic approach.

Adult↗

Sodium dodecyl sulfate and C31G as microbicidal alternatives to nonoxynol 9: comparative sensitivity of primary human vaginal keratinocytes.

A broad-spectrum vaginal microbicide must be effective against a variety of sexually transmitted disease pathogens and be minimally toxic to the cell types found within the vaginal epithelium, including vaginal keratinocytes. We assessed the sensitivity of primary human vaginal keratinocytes to potential topical vaginal microbicides nonoxynol-9 (N-9), C31G, and sodium dodecyl sulfate (SDS). Direct immunofluorescence and fluorescence-activated cell sorting analyses demonstrated that primary vaginal keratinocytes expressed epithelial cell-specific keratin proteins. Experiments that compared vaginal keratinocyte sensitivity to each agent during a continuous, 48-h exposure demonstrated that primary vaginal keratinocytes were almost five times more sensitive to N-9 than to either C31G or SDS. To evaluate the effect of multiple microbicide exposures on cell viability, primary vaginal keratinocytes were exposed to N-9, C31G, or SDS three times during a 78-h period. In these experiments, cells were considerably more sensitive to C31G than to N-9 or SDS at lower concentrations within the range tested. When agent concentrations were chosen to result in an endpoint of 25% viability after three daily exposures, each exposure decreased cell viability at the same constant rate. When time-dependent sensitivity during a continuous 48-h exposure was examined, exposure to C31G for 18 h resulted in losses in cell viability not caused by either N-9 or SDS until at least 24 to 48 h. Cumulatively, these results reveal important variations in time- and concentration-dependent sensitivity to N-9, C31G, or SDS within populations of primary human vaginal keratinocytes cultured in vitro. These investigations represent initial steps toward both in vitro modeling of the vaginal microenvironment and studies of factors that impact the in vivo efficacy of vaginal topical microbicides.

Anti-Infective Agents↗

Inactivation of human immunodeficiency virus type 1 by nonoxynol-9, C31G, or an alkyl sulfate, sodium dodecyl sulfate.

A highly desirable approach to prevention of human immunodeficiency virus type 1 (HIV-1) transmission during sexual intercourse is the development of nontoxic, topical, broad spectrum microbicides effective against transmission of cell-associated and cell-free virus. Toward this end, the HIV-1 inactivation potential of surface active agents C31G and an alkyl sulfate, sodium dodecyl sulfate (SDS) was assessed. Because of its extensive use as a microbicidal agent, nonoxynol-9 (N-9) was used as a reference against which C31G and SDS were compared. Viral inactivation was measured using HIV-1 LTR-beta-galactosidase indicator cells (expressing CD4 or CD4/CCR5) derived from HeLa cells, a cell line of human cervical adenocarcinoma origin. In experiments which examined inactivation of cell-free HIV-1, C31G was generally more effective than N-9. Viral inactivation by SDS occurred at twice the concentration necessary to achieve similar levels of inactivation using either N-9 or C31G. Using HeLa and HeLa-derived cells in cytotoxicity studies, it was demonstrated that SDS is as much as 11 and five times less cytotoxic than N-9 or C31G, respectively, during 48 h of continuous exposure. SDS (unlike C31G and N-9) can inactivate non-enveloped viruses such as human papillomavirus (HPV) [Howett, M.K., Neely, E.B., Christensen, N.D., Wigdahl, B., Krebs, F.C., Malamud, D., Patrick, S.D., Pickel, M.D., Welsh, P.A., Reed, C.A., Ward, M.G., Budgeon, L.R., Kreider, J.W., 1999. A broad-spectrum microbicide with virucidal activity against sexually transmitted viruses. Antimicrob. Agents Chemother. 43(2), 314-321]. Since addition of SDS to C31G or N-9 may make the resulting microbicidal mixtures broadly effective against both enveloped and non-enveloped viruses, several surface active agent combinations were evaluated for their abilities to inactivate HIV-1. Addition of SDS to either C31G or N-9 resulted in mixtures that were only slightly less effective than equivalent concentrations of C31G or N-9 alone. To investigate inactivation of cell-associated infectivity, HIV-1 IIIB-infected SupT1 cells were treated with N-9, C31G, or SDS. Inactivation of cell-associated infectivity required higher microbicide concentrations than were needed for inactivation of cell-free virus. However, the relative activities of N-9, C31G, or SDS were similar to those seen in assays of inactivation using cell-free virus. These studies suggest that C31G and SDS may be attractive candidates for human trials as topical microbicides effective against HIV-1 transmission since both function at concentrations that provide effective viral inactivation with low levels of cytotoxicity. SDS microbicides (used alone or with other microbicides) may provide the added advantage of protection from HPV infection.

Anti-HIV Agents↗

Bilateral tinea nigra plantaris and tinea nigra plantaris mimicking melanoma.

Tinea nigra, a superficial fungal infection caused by Phaeoannellomyces werneckii, presents as a hyperpigmented, nonscaling macule of variable size and shape. Typically lacking induration, erythema, or pruritus, these "ink spot" lesions may resemble junctional nevi or malignant melanoma. Rapid, noninvasive diagnosis can be provided by potassium hydroxide examination, demonstrating numerous large, dematiaceous hyphae.

Adult↗

Delayed cellulitis associated with conservative therapy for breast cancer.

BACKGROUND AND OBJECTIVES: Delayed breast cellulitis is an infrequently reported entity after conservation therapy for breast cancer. We describe our experience with this entity at Naval Medical Center, San Diego. METHODS: Eight patients who presented with delayed cellulitis after wide local excision/axillary dissection and breast radiotherapy (RT) are presented. Their clinical characteristics and therapy are described and possible causative factors are analyzed. RESULTS: The latency of breast cellulitis is variable after breast conservation therapy, although most cases in our experience and in the literature occur within a year post-RT. These infections are frequently refractory to a single course of antibiotics (n = 4 cases in our experience). Some patients suffer multiple episodes separated by months. CONCLUSIONS: Breast cancer patients are at risk for delayed cellulitis after conservative surgery and RT. The mechanism of such events probably involves lymph stasis, however, therapy is no different from the more frequently occurring cases of cellulitis presenting perioperatively.

Aged↗

The impact of price labeling of muscle relaxants on cost consciousness among anesthesiologists.

STUDY OBJECTIVE: To determine whether placing price labels on the vial caps of muscle relaxants increases cost consciousness among anesthesiologists. DESIGN: Retrospective study. SETTING: University hospital departments of anesthesia and pharmacy. MEASUREMENTS AND MAIN RESULTS: We placed price labels on the vial caps of all muscle relaxants for a study period of 1 year. At the beginning of the investigation, we informed the anesthesiologists of the study, discussed the prices for different muscle relaxants, and encouraged utilizing less expensive muscle relaxants whenever possible without compromising patient care. The price labels on the vial caps served as visual reminders of the various costs of muscle relaxants during daily practice. We compared the total amount spent on each muscle relaxant during the period from October 1993 to September 1994 with the period from October 1994 to September 1995. The total number of surgical cases from October 1993 to September 1994 and from October 1994 to September 1995 was unchanged and equaled 20,389 and 20,358 cases, respectively. Expenditures for pancuronium increased 104.1%. Total expenditure decreased by 12.5%, with a net savings of $47,111. CONCLUSION: Expenditures for the less costly pancuronium increased while expenditures for vecuronium and atracurium decreased. Price labeling of muscle relaxants in conjunction with education reduces total pharmacy expenditure on muscle relaxants.

Androstanols↗

(Aryloxy)alkylamines as selective human dopamine D4 receptor antagonists: potential antipsychotic agents.

The discovery of a series of novel (aryloxy)alkylamines with selective affinity for the dopamine D4 receptor is described. Target compounds were tested for binding to cloned human dopamine D2, D3, and D4 receptor subtypes expressed in Chinese hamster ovary (CHO) K-1 cells. A number of compounds demonstrated subnanomolar Ki values for binding to the D4 receptor, with several 100-fold selectivities toward the D2 and D3 receptors. Several compounds with combined D3/D4 receptor binding selectivity were also identified. A limited structure-activity relationship study of this chemical series is discussed. In a mitogenesis functional assay, the effect of the test compounds on cellular uptake of [3H]thymidine in D4-transfected CHO 10,001 cells was measured and compared to the response of the full dopamine agonist quinpirole. The activity of the compounds varied from full antagonist to weak partial agonist activity (intrinsic activity of 0-19% in comparison to quinpirole).

Animals↗

Chromeno[3,4-c]pyridin-5-ones: selective human dopamine D4 receptor antagonists as potential antipsychotic agents.

The discovery of a series of chromeno[3,4-c]pyridin-5-ones with selective affinity for the dopamine D4 receptor is described. Target compounds were tested for binding to cloned human dopamine D2, D3, and D4 receptor subtypes expressed in Chinese hamster ovary (CHO) K-1 cells. Several compounds demonstrated single digit nanomolar Ki values for binding to the D4 receptor with several hundred-fold selectivities toward the D2 and D3 receptors. A limited SAR study of this series is discussed. In a mitogenesis assay measuring [3H]thymidine uptake, the target compounds showed antagonist to weak partial agonist activity at the D4 receptor, with intrinsic activities ranging from 0 to 35%. Compound 6, 3-benzyl-8-methyl-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one, increased DOPA (L-3,4-dihydroxyphenylalanine) synthesis 84% in the hippocampus and 10% in the striatum of rat brain when dosed orally at 10 mg/kg.

Animals↗

Primary sternal osteomyelitis.

A case report of primary sternal osteomyelitis, a rare clinical entity, is presented. Treatment of primary sternal osteomyelitis is antibiotics and complete debridement of the infected bone and anterior periosteum. If the posterior sternal periosteum is not involved, it should be left intact. The defect can be covered with skeletal muscle flaps, which improves healing and minimizes recurrence. This approach led to a complete and timely cure.

Adult↗

Gas chromatographic-mass spectrometric determination of urinary 1-aminocyclopropanecarboxylic acid in mice using a deuterated internal standard.

A gas chromatographic-mass spectrometric method is described for the determination of 1-aminocyclopropanecarboxylic acid in mouse urine using the 2,2,3,3-[2H4] isotopolog as an internal standard. Samples (0.1 ml) were extracted using an exchange resin, then derivatized with pentafluoropropanol and pentafluoropropionic anhydride at 100 degrees C for 25 min. Gas chromatography was performed on a (5% phenyl)methylpolysiloxane column and detection was by selected-ion monitoring of M-CO2CH2CF2CF3 fragment ions. The method provided high response linearity (mean r = 0.999) and precision (< 5% coefficient of variation). After orally dosing mice with 1-aminocyclopropanecarboxylic acid (300 mg/kg), 46 and 10% of the dose was excreted unchanged in the 0-24 h and 24-48 h urines, respectively.

Amino Acids↗

Determination of plasma cocaine and ethylcocaine (cocaethylene) in mice using gas chromatography-mass spectrometry and deuterated internal standards.

A gas chromatographic-mass spectrometric method is described for the determination of cocaine and ethylcocaine (cocaethylene) from mouse plasma microsamples (50 microliters). [2H3]Cocaine and [2H5]ethylcocaine served as internal standards, analytical separations were performed on a (5% phenyl)methylpolysiloxane capillary column, and detection was by selected-ion monitoring of electron-impact generated fragment ions [M - CO2Ph]. Pilot study plasma concentrations of ethylcocaine following coadministration of cocaine and ethanol were less than 5% of the parent drug.

Animals↗

Gas chromatographic-mass spectrometric determination of plasma and brain cocaine in mice.

A gas chromatographic-mass spectrometric method is described for the determination of cocaine in mouse plasma microsamples and brain. Cocaine and [2H3]cocaine were extracted with pentane-isopropyl alcohol (97:3, v/v), chromatographed on a (5% phenyl) methylpolysiloxane capillary column, and detected by selected-ion monitoring of electron impact generated m/z 182 and 185 fragment ions. The small sample size (50 microliters), simplicity of workup, and high response linearity (mean r = 0.9993) distinguish the method. Cocaine was found in mouse brain at approximately 5 times greater concentration than in plasma after 20 or 40 mg/kg subcutaneous doses.

Animals↗

Biocontainment design considerations for biopharmaceutical facilities.

This article highlights biocontainment design considerations for biopharmaceutical manufacturing facilities. The major focus of this report is on industry's use and interpretation of the regulations with specific design recommendations for a Biosafety Level 2--Large-Scale physical containment level as described by the National Institutes of Health Guidelines.

Accidents, Occupational↗

Attitudes toward genetic testing of Amish, Mennonite, and Hutterite families with cystic fibrosis.

BACKGROUND: We had the unique opportunity to study families with cystic fibrosis (CF) from an interrelated Amish-Mennonite kindred and from an isolated Hutterite kindred. METHODS: While obtaining blood for DNA linkage analysis to help find the CF gene, we asked family members to answer a questionnaire about attitudes and feelings toward genetic testing. The questionnaire was also administered to families receiving care at the University of Rochester. After DNA-based CF carrier testing was developed, we asked the families whether they wanted to know the results. RESULTS: Each cultural group felt differently about many issues. Between 31% and 78% approved of CF-carrier testing and 14% to 78% approved of prenatal diagnosis. The majority (59%) of Hutterite parents and siblings were opposed to carriers marrying carriers and most (82%) of the CF families wanted to know the results of carrier testing. CONCLUSIONS: Cultural differences need to be understood before genetic services are offered. Also, most CF mutations and their clinical correlates (phenotypes) will need to be defined. There are as few as three CF mutations in the Hutterite population. It will be possible to offer them the option to choose accurate genetic counseling. It will be difficult to offer genetic services to other populations with more heterogeneous attitudes and many more identified and yet-to-be-identified CF mutations.

Abortion, Therapeutic↗

Advances in the management of hemorrhagic shock.

The Scientific Board of the California Medical Association presents the following inventory of items of progress in general surgery. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in general surgery that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on General Surgery of the California Medical Association, and the summaries were prepared under its direction.

Humans↗